title: Ceragenin CSA-13 induces cell cycle arrest and antiproliferative effects in wild-type and p53 null mutant HCT116 colon cancer cells.
abstract: Antimicrobial peptides of the cathelicidin family play a central role in the host defense system. Our group has reported previously that cathelicidin-related or cathelicidin-modified antimicrobial peptides, such as FF/CAP-18, have antiproliferative effects on the squamous cell carcinoma cell line SAS-H1 and colon cancer-derived cell line HCT116. Ceragenin CSA-13, which mimics the hydrophobic and cationic morphology of cathelicidin-related peptides, was developed to reduce synthetic costs and resolve stability issues in the presence of proteases. In this study, we evaluated the antiproliferative effect of CSA-13 on HCT116 cells. We evaluated the effects of CSA-13 in HCT116 cells by measuring cell growth, detecting apoptosis, analyzing the cell cycle, and examining mitochondrial membrane depolarization. Treatment with CSA-13 suppressed HCT116 cell proliferation in a dose-dependent manner, increasing the incidence of apoptosis detected by the binding of Annexin V. Furthermore, cell cycle analysis showed that the cell cycle of CSA-13-treated wild-type and p53 null mutant HCT116 cells was arrested at the G1/S phase, indicating that CSA-13 affects the cell cycle by a p53-independent pathway. Our study showed that CSA-13 exerts an antiproliferative effect in cancer cells similar to that of FF/CAP-18, suggesting that membrane-permeabilizing capability is the common underlying mechanism for anticancer and antimicrobial effects of CSA-13 and anitimicrobial peptides.
authors.affiliation: Laboratory of Animal Microbiology, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.
authors.forename: Kengo
authors.initials: K
authors.lastname: Kuroda
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Fukuda
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Okumura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoneyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Isogai
authors.forename: Paul B
authors.initials: PB
authors.lastname: Savage
authors.forename: Emiko
authors.initials: E
authors.lastname: Isogai
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D045325:HCT116 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009154:Mutation; D013256:Steroids / Q000494:pharmacology*; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D013256:Steroids; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; C521528:ceragenin CSA-13; D020169:Caspases